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Title: RhoE interferes with Rb inactivation and regulates the proliferation and survival of the U87 human glioblastoma cell line

Abstract

Rho GTPases are important regulators of actin cytoskeleton, but they are also involved in cell proliferation, transformation and oncogenesis. One of this proteins, RhoE, inhibits cell proliferation, however the mechanism that regulates this effect remains poorly understood. Therefore, we undertook the present study to determine the role of RhoE in the regulation of cell proliferation. For this purpose we generated an adenovirus system to overexpress RhoE in U87 glioblastoma cells. Our results show that RhoE disrupts actin cytoskeleton organization and inhibits U87 glioblastoma cell proliferation. Importantly, RhoE expressing cells show a reduction in Rb phosphorylation and in cyclin D1 expression. Furthermore, RhoE inhibits ERK activation following serum stimulation of quiescent cells. Based in these findings, we propose that RhoE inhibits ERK activation, thereby decreasing cyclin D1 expression and leading to a reduction in Rb inactivation, and that this mechanism is involved in the RhoE-induced cell growth inhibition. Moreover, we also demonstrate that RhoE induces apoptosis in U87 cells and also in colon carcinoma and melanoma cells. These results indicate that RhoE plays an important role in the regulation of cell proliferation and survival, and suggest that this protein may be considered as an oncosupressor since it is capable to inducemore » apoptosis in several tumor cell lines.« less

Authors:
 [1];  [2];  [1];  [1];  [2];  [2];  [3];  [4]
  1. Departamento de Quimica, Bioquimica y Biologia Molecular, Universidad Cardenal Herrera-CEU, Valencia (Spain)
  2. Laboratorio de Patologia Celular, Centro de Investigacion Principe Felipe, Valencia (Spain)
  3. Departamento de Quimica, Bioquimica y Biologia Molecular, Universidad Cardenal Herrera-CEU, Valencia (Spain). E-mail: iperez@uch.ceu.es
  4. Laboratorio de Patologia Celular, Centro de Investigacion Principe Felipe, Valencia (Spain). E-mail: guasch@cipf.es
Publication Date:
OSTI Identifier:
20972119
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 313; Journal Issue: 4; Other Information: DOI: 10.1016/j.yexcr.2006.11.006; PII: S0014-4827(06)00478-2; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACTIN; ADENOVIRUS; APOPTOSIS; CELL PROLIFERATION; GLIOMAS; LARGE INTESTINE; MELANOMAS; MICROTUBULES; PHOSPHORYLATION; TUMOR CELLS

Citation Formats

Poch, Enric, Minambres, Rebeca, Mocholi, Enric, Ivorra, Carmen, Perez-Arago, Amparo, Guerri, Consuelo, Perez-Roger, Ignacio, and Guasch, Rosa M. RhoE interferes with Rb inactivation and regulates the proliferation and survival of the U87 human glioblastoma cell line. United States: N. p., 2007. Web. doi:10.1016/j.yexcr.2006.11.006.
Poch, Enric, Minambres, Rebeca, Mocholi, Enric, Ivorra, Carmen, Perez-Arago, Amparo, Guerri, Consuelo, Perez-Roger, Ignacio, & Guasch, Rosa M. RhoE interferes with Rb inactivation and regulates the proliferation and survival of the U87 human glioblastoma cell line. United States. doi:10.1016/j.yexcr.2006.11.006.
Poch, Enric, Minambres, Rebeca, Mocholi, Enric, Ivorra, Carmen, Perez-Arago, Amparo, Guerri, Consuelo, Perez-Roger, Ignacio, and Guasch, Rosa M. Thu . "RhoE interferes with Rb inactivation and regulates the proliferation and survival of the U87 human glioblastoma cell line". United States. doi:10.1016/j.yexcr.2006.11.006.
@article{osti_20972119,
title = {RhoE interferes with Rb inactivation and regulates the proliferation and survival of the U87 human glioblastoma cell line},
author = {Poch, Enric and Minambres, Rebeca and Mocholi, Enric and Ivorra, Carmen and Perez-Arago, Amparo and Guerri, Consuelo and Perez-Roger, Ignacio and Guasch, Rosa M.},
abstractNote = {Rho GTPases are important regulators of actin cytoskeleton, but they are also involved in cell proliferation, transformation and oncogenesis. One of this proteins, RhoE, inhibits cell proliferation, however the mechanism that regulates this effect remains poorly understood. Therefore, we undertook the present study to determine the role of RhoE in the regulation of cell proliferation. For this purpose we generated an adenovirus system to overexpress RhoE in U87 glioblastoma cells. Our results show that RhoE disrupts actin cytoskeleton organization and inhibits U87 glioblastoma cell proliferation. Importantly, RhoE expressing cells show a reduction in Rb phosphorylation and in cyclin D1 expression. Furthermore, RhoE inhibits ERK activation following serum stimulation of quiescent cells. Based in these findings, we propose that RhoE inhibits ERK activation, thereby decreasing cyclin D1 expression and leading to a reduction in Rb inactivation, and that this mechanism is involved in the RhoE-induced cell growth inhibition. Moreover, we also demonstrate that RhoE induces apoptosis in U87 cells and also in colon carcinoma and melanoma cells. These results indicate that RhoE plays an important role in the regulation of cell proliferation and survival, and suggest that this protein may be considered as an oncosupressor since it is capable to induce apoptosis in several tumor cell lines.},
doi = {10.1016/j.yexcr.2006.11.006},
journal = {Experimental Cell Research},
number = 4,
volume = 313,
place = {United States},
year = {Thu Feb 15 00:00:00 EST 2007},
month = {Thu Feb 15 00:00:00 EST 2007}
}